Discovery of Novel Pyrazole Carboxylate Derivatives Containing Thiazole as Potential Fungicides

• Published in: Journal of agricultural and food chemistry 2021-08, Vol.69 (30), p.8358-8365
• Main Authors: Xia, Dongguo, Cheng, Xiang, Liu, Xiaohang, Zhang, Chengqi, Wang, Yunxiao, Liu, Qiaoyun, Zeng, Qi, Huang, Niqian, Cheng, Yao, Lv, Xianhai
• Format: Article
• Language: English
• Subjects: Agricultural and Environmental Chemistry
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.1c01189

Inspired by commercially established fluxapyroxad as the lead compound of novel efficient antifungal ingredients, novel pyrazole carboxylate derivatives containing a flexible thiazole backbone were successfully designed, synthesized, and detected for their in vitro and in vivo biological activities against eight agricultural fungi. The antifungal bioassay results showed that compound 24 revealed excellent bioactivities against Botrytis cinerea and Sclerotinia sclerotiorum, with median effective concentrations (EC50) of 0.40 and 3.54 mg/L, respectively. Compound 15 revealed remarkable antifungal activity against Valsa mali, with an EC50 value of 0.32 mg/L. For in vivo fungicide control against B. cinerea and V. mali, compounds 3 and 24 at 25 mg/L, respectively, displayed prominent efficacy on cherry tomatoes and apple branches. Molecular docking results demonstrated that compound 15 could form an interaction with several crucial residues of succinate dehydrogenase (SDH), and the in vitro enzyme assay indicated that the target compound 15 displayed an inhibitory effect toward SDH, with an IC50 value of 82.26 μM. The experimental results indicated that phenyl pyrazole carboxylate derivatives displayed a weak antifungal property and low activity compared to the other title substituent pyrazole carboxylate derivatives. Compounds 3, 15, and 24 are promising antifungal candidates worthy of further fungicide development due to their prominent effectiveness.